(Introduction)

- The immune system: a new look at pain

(Introduction)

Pain can be defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. It is a response triggered by nociceptive inputs from the periphery that are transmitted centrally to the spinal cord and then ascend through the paleospinothalamic tracts to limbic structures.

Pain can be clinically classified as either nociceptive or neuropathic, although in practice these may coexist.1 Nociceptive pain arises from mechanical, chemical or thermal irritation of peripheral sensory nerves (e.g., after surgery or trauma or associated with degenerative processes such as osteoarthritis). Typically, the nociceptive pain is described as sharp and well localized. However, neuropathic pain has quite different clinical features with poor localization and is defined as pain initiated or caused by a primary lesion or dysfunction in the nervous system such as post-herpetic neuralgia and painful diabetic neuropathy. The neuropathic pain is often associated with the appearance of abnormal sensory signs with clinical characteristics of allodynia (pain as a result of a stimulus which does not normally provoke pain) and/or hyperalgesia (an increased response to a stimulus which is normally painful).2

Pain is generally considered as purely neural phenomenon that reflects the changes in dorsal horn neuronal excitability of the spinal cord by afferent inputs. A chain of neurons carries the pain message from the injury to the spinal cord, and then from the spinal cord up to consciousness in the brain.

It is now recognized that pain and its modulation are not solely mediated by neurons but also involved in neuroimmune interaction.3-5 The first idea about the dynamic inter-relationships of the central nervous system and immune system arose from studies on the cascade of events initiated by exposure to stressors.6 The immune system is obviously involved especially when nerve damage is due to an infectious process such as herpes zoster or an autoimmune condition such as Guillain-Barre syndrome. And it is crucially important to note that the immune system also involves in a completely sterile nerve injury, because the cellular debris is a potent immune stimulus. Non-neuronal cells include immune cells in the periphery and glia within the brain and spinal cord.

In order to identify novel therapeutics for pain and, in particular, to design compounds for clinical use in “mechanism based” treatment paradigms, it is important to understand the underlying pathophy- siology of pain.